7-Azaspiro[3.5]nonane-2,7-dicarboxylic acid, 7-(1,1-dimethylethyl) ester

Uses

7-(tert-Butoxycarbonyl)-7-azaspiro[3.5]nonane-2-carboxylic Acid is used as a reagent in the preparation of mineralocorticoid receptor agonists.

Synthesis

The general procedure for the synthesis of 7-(tert-butoxycarbonyl)-7-azaspiro[3.5]nonane-2-carboxylic acid using tert-butyl 2-cyano-7-azaspiro[3.5]nonane-7-carboxylate as a starting material was as follows: tert-butyl 2-cyano-7-azaspiro[3.5]nonane-7-carboxylate (1.5 g, 5.99 mmol) was dissolved in ethanol (40 mL) and water (40 mL) in a solvent mixture of ethanol (40 mL) and water (40 mL). Lithium hydroxide (880 mg, 21 mmol) was added to this solution and the reaction mixture was subsequently heated to reflux and held for 4 hours. After completion of the reaction, the mixture was cooled to room temperature. Ethanol was removed by rotary evaporator and the remaining aqueous phase was adjusted to pH 1-2 with 6N hydrochloric acid. next, the aqueous phase was extracted with ether. The organic layers were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, filtered and concentrated to give 7-(tert-butoxycarbonyl)-7-azaspiro[3.5]nonane-2-carboxylic acid (1.6 g, 99% yield) as a white solid. The product was characterized by 1H NMR (400 MHz, CDCl3): δ 3.34-3.41 (m, 2H), 3.27-3.34 (m, 2H), 3.10-3.21 (m, 1H), 2.12 (d, J = 8.9 Hz, 4H), 1.58-1.63 (m, 2H), 1.52-1.58 (m, 2H), 1.47 ( s, 9H). Mass spectral analysis showed m/z 214 ([MH - t-Bu]+), 292 ([MNa]+).

References

[1] Patent: US2010/113465, 2010, A1. Location in patent: Page/Page column 32